Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
Org Biomol Chem. 2021 May 26;19(20):4515-4519. doi: 10.1039/d1ob00238d.
Pantothenate synthetase from Escherichia coli (PSE. coli) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B5), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (R)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PSE. coli enabled the efficient synthesis of pharmaceutically-relevant vitamin B5 antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
来自大肠杆菌的泛酸合酶（PSE. coli）催化（R）-泛酸和β-丙氨酸与 ATP 的依赖作用，生成（R）-泛酸（维生素 B5），这是辅酶 A 的生物合成前体。本文表明，除了天然的胺底物β-丙氨酸外，该酶还接受广泛的结构多样的胺，包括 3-氨基-2-氟丙酸、4-氨基-2-羟基丁酸、4-氨基-3-羟基丁酸和色胺，与天然羧酸底物（R）-泛酸偶联生成酰胺产物，转化率高达>99%。PSE. coli 的广泛的胺底物范围使得具有优异的分离收率（高达 89%）的药物相关维生素 B5 抗代谢物的高效合成成为可能。这种生物催化的酰胺合成策略可能有助于寻找针对辅酶 A 生物合成和利用的新型抗生素。
